Polish Patent No 125 995 and A Journal of Applied Polymer Science” vol. 33 p. 177, 1987 teach a method, to produce a chitosan with a developed internal surface in a batch process in which the chitosan is periodically precipitated from its solutions in aqueous organic or inorganic acids or their salts by means of hydroxides of alkali metals. The mixture is vigorously stirred. The precipitated chitosan in suspension form is washed with water several times. The well-known method produces chitosan with a developed internal surface with an out-put of 70-90% of theoretical values. The batch process requires at least 12-24 hours for a production cycle. The single batches of the product lack homogeneity. The product tends to degrade and its sorption capacity is rather poor, due to insufficient development of the inner surface. Polish Patent 164 247 and Finnish Patent FI 83 426 teach continuous methods to produce microcrystalline chitosan (MCCh). A solution of chitosan in aqueous acids and/or their salts is introduced to a reactor along with an aqueous hydroxide solution of alkali metals and/or their salts until microcrystalline chitosan is formed at pH>7. Simultaneously, the microcrystalline alkaline suspension of chitosan is continuously removed from the reactor. The alkaline solution may also be introduced directly to the recirculation system. Limitations of the process are: out-put below 90%, average agglomerate size above 1 μm and water retention value below 5000%.
Water retention value is an indication of the development of the inner surface. Another drawback of these processes is that it is not possible to control the molecular, and super molecular and morphological structure of the generated chitosan. The continuous process causes a substantial decrease of the average molecular weight of the generated MCCh as result of intensive degradation processes.
Polish Patent Application P 340 132 and the International Application WO 01/87 988 teach a method to produce modified microcrystalline chitosan. According to the disclosed process, a chitosan solution in aqueous solutions of acids and/or their salts with the polymer concentration not lower than 0.001 wt % is neutralized with aqueous hydroxides and/or their salts with a concentration in the range of 0.01-20% at intensive agitation with a rotary speed 10-1000 rpm to attain pH in the range 5.0-6.9; the chitosan salt is thereby converted into its gel form. The gel is homogenized at agitation speed in the range of 100-5000 rpm for not shorter than 10 seconds. Next, still with agitation 100-5000 rpm, the gel is alkalized with aqueous hydroxides in the concentration of 0.01-20 wt % to pH not lower than 6.9. The produced gel-like microcrystalline chitosan suspension is purified, possibly concentrated and dried according to known procedures. This method does not enable production of a modified microcrystalline chitosan with controlled molecular, super-molecular and morphological structure and assumed properties, particularly biological ones.
The invention also concerns a chitosan-calcium complex and a method to produce the complex. The sorption of metal ions by chitosan in its solid state or in aqueous organic and inorganic acid solutions in is well-known from following publications: journals-International Journal of Biological Macromolecules, v. 9, p. 109, 1987, “Carbohydrate Polymer”, v. 8, p. 1-21, 1988, v. 11, p. 205-307, 1989; “Talanta”, v. 16, p. 1571-1579, 1969; “Carbohydrate Polymers”, v. 36, p. 267-276, 1998 and monographs “Chitin Chemistry”, Mac Millan Press Ltd, Great Britain, 1992, p. 222-225 and “Advances in Chitin Science”, v. IV, Universitat Potsdam, Germany, 2000, p. 202-205.
The amount of bound calcium (II) ions is insignificant compared to other alkali metals and amounts to only 0.4-0.8×10−3 mol/gr of chitosan. Soluble derivatives of chitosan demonstrate a better ability to bind calcium II ions notably carboxymethylchitosan, carboxybenzylchitosan, (N)methylchitosan phosphoniate. Complexes of these derivatives with calcium II ions do not dissolve in water. Unknown are chitosan complexes with calcium (II) ions able to dissolve in water or to produce thermally stable suspensions.